title: Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans.
abstract: Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness. We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes. We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.forename: Ersan
authors.initials: E
authors.lastname: Kalay
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Mosrati
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Mounira
authors.initials: M
authors.lastname: Hmani-Aifa
authors.forename: Hanka
authors.initials: H
authors.lastname: Venselaar
authors.forename: Mayya N
authors.initials: MN
authors.lastname: Kawar
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Tlili
authors.forename: Bert
authors.initials: B
authors.lastname: van der Zwaag
authors.forename: Shahid Y
authors.initials: SY
authors.lastname: Khan
authors.forename: Leila
authors.initials: L
authors.lastname: Ayadi
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Morell
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfedine
authors.forename: Refik
authors.initials: R
authors.lastname: Caylan
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostrik
authors.forename: Ahmet
authors.initials: A
authors.lastname: Karaguzel
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism; D005190:Family; D008040:Genetic Linkage; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D017433:Protein Structure, Secondary; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016364:Reading Frames / Q000235:genetics*; D026801:Synteny / Q000235:genetics
chemical_list: C533107:LRTOMT protein, human; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D002334:Carnitine O-Palmitoyltransferase